Implantable cardiac stimulation devices are well known in the art. They may take the form of implantable defibrillators or cardioverters which treat accelerated rhythms of the heart, such as fibrillation, or implantable pacemakers which maintain the heart rate above a prescribed limit, such as, for example, to treat a bradycardia. Implantable cardiac devices are also known which incorporate both a pacemaker and a defibrillator.
As seen on a standard electrocardiogram (ECG), one complete heartbeat includes a P-wave, a QRS complex, and a T-wave. In a normal cardiac cycle, the atria depolarize and contract (P-waves), delivering blood into the relaxed ventricles. The atria now repolarize and relax while the ventricles, now filled to capacity with blood, depolarize, contract and pump (QRS complex) blood into the systemic and pulmonary circulation systems. The ventricles then repolarize and relax (T-wave). The cycle begins again at the end of ventricular repolarization with the onset of passive ventricular filling. The “QT” interval is measured from the onset of the QRS complex to the end of the visible T-wave on the surface ECG. The QT interval is generally accepted as an indirect measure of patient myocardial depolarization and repolarization. The QT interval prolongation may occur naturally during sleep, or by a variety of drugs, electrolyte imbalance, central nervous system disorders, metabolic abnormalities, bradycardia, ischemia and other intrinsic disease states.
The lengthening in the QT interval is associated with increased temporal dispersion of myocardial refractoriness which sets the stage for local reentry and initiation of life threatening ventricular arrhythmias, including Torsade de Pointe (TdP), ventricular fibrillation, often leading to syncope and sudden cardiac death. Of particular interest, the ventricular tachyarrhythmia known as Torsade de Pointe is unique: it is not a uniform shape, but shows a cyclic change in morphology in that the QRS complexes appear to be turning around a point.
For patients who develop acquired Long QT Syndrome (LQTS), the treatment typically is correction of the underlying metabolic abnormality or withdrawal from the medication that has initiated this problem. Until the problem is reversed, temporary cardiac pacing at a relative fast, fixed rate is commonly utilized to stabilize the rhythm and prevent the TdP. Sometimes, intravenous magnesium sulfate is also utilized.
There is also a condition known as Congenital LQTS. To date, five separate genetic abnormalities have been identified as causes of this condition in various individuals. Congenital LQTS is associated with sudden death in adolescents and young adults. Part of this syndrome involves an imbalance in the sympathetic neural innervation of the heart. Hence, one approach to treating this condition is the use of beta adrenergic receptor blocking drugs (beta blockers) to correct the intrinsic imbalance of neural innervation to the heart. However, this is associated with further slowing of the heart rate, which has a negative effect of lengthening the QT interval.
In patients with congenital LQTS whose heart rate has slowed with beta blockers or who have been shown to have a significant shortening of their QT interval with higher heart rates, permanent pacing has been used. In this setting, the base rate of the pacemaker is set to a fixed rate of about 80 or 90 bpm. Unfortunately, there is also evidence that pacing at a relatively high rate may be associated with progressive ventricular dysfunction. It is known, for example, that intrinsic sustained or incessant tachycardias may cause a cardiomyopathy. Hence, keeping the heart rate elevated at such a fixed rate, and never allowing it to decrease in accordance with a physiologic diurnal variation, may be counterproductive on a long term basis.
It is also known that QT interval varies diurnally, having a first level during the daytime and a second level during sleep associated with, but independent of, a slower heart rate. The QT interval is further known to shorten due to exercise, and circulating catecholamines, and further shortens due to increased heart rates. These fluctuations make it an unattractive sensor to be used alone for predicting the patient's vulnerability to tachyarrhythmias. For example, U.S. Pat. No. 6,370,431 suggests that “QT prolongation by itself is likely, for most patients, to be an insufficient predictor of the true onset of TdP or another ventricular arrhythmia”, and instead seeks to find secondary indicators to predict true onset.
It is also known that there is a higher incidence of tachyarrhythmias in the early morning hours, which may be due to the inability of the patient's heart to resume a normal QT interval upon wakening. Couple this condition with premature ventricular beats that may arise due to the changes in activation-recovery states of the tissue, and the stage is set for VT, VF and sudden cardiac death.
As mentioned above, the QT interval has been used to detect sleep-wake states (see for example, U.S. Pat. No. 5,861,011, Stoop). However, in patients with abnormally long QT intervals and LQTS, monitoring the QT interval by itself may not be an accurate or reliable indicator of sleep-wake states. Furthermore, it is reported that the QT interval is believed to be unreliable in the presence of bundle branch block.
Rate smoothing is a mode of pacing that has used to prevent the relative bradycardia associated with the pauses, which follow a premature ventricular contraction (PVC). This relative bradycardia has also been shown to exacerbate the QT interval lengthening and results in a worsening of the arrhythmias.
Where pacing is not totally effective, or there is a history of sudden death in family members, an increasing number of physicians are recommending an implantable cardioverter defibrillator (ICD). While an ICD provides absolute rescue therapy, it is painful. In addition, if the ICD is used to provide high rate bradycardia pacing, this will significantly shorten the projected longevity of the ICD.
Hence, there is a need in the art for a more effective treatment of abnormally long QT interval such as that associated with LQTS. The present invention provides an implantable cardiac stimulation device capable for providing such therapy.